The overall goal of this project is to quantitatively understand the rules that govern the induction and expression of long-term plasticity at neocortical synapses. Altering sensory experience, both during development and in the adult, can lead to potent changes in the organization of cortical receptive fields. A common theme of these plasticity experiments is that neurons representing parts of the periphery which are stimulated together become strengthened and linked, while neurons representing parts of the periphery which are lesioned or stimulated in an uncorrelated fashion become weakened and disconnected. Depending on the paradigm, many mechanisms, both within the cortex and more peripherally may contribute, but it is widely assumed that Hebbian plasticity at cortical synapses is a key component of experience-dependent changes in sensory representation. Despite the attractiveness of this idea, it has been difficult to formulate in a rigorous and quantitative way. A quantitative formulation requires that we know not merely that "neurons that fire together wire together," but exactly how much firing at what frequency and with what degree of correlation are required. To that end we will systematically vary the rate and timing with which pre- and postsynaptic neurons fire during paired recording in neocortical slices. Based on these recordings, we will develop a comprehensive and predictive picture of the rules governing the induction and expression of long term plasticity at synapses between thick-tufted layer 5 pyramidal neurons. In addition we will make whole cell recordings from neurons in the somatosensory cortex in vivo and determine whether or not the rules measured in slices also apply to synaptic responses evoked electrically or by stimulating the facial whiskers. The results of this basic research on the link between cortical synaptic plasticity and the reorganization of somatosensory representations may provide clues that will be useful in treating derangements of cortical plasticity during dementia or in promoting recovery of function following brain injury or stroke.